DESCRIPTION: (Applicant's Abstract) The long-term goal of this project is to contribute to the understanding of dendritic mechanisms underlying synaptic integration and plasticity. These fundamental cellular processes play an important role in the more global mechanisms of information processing, learning and memory. In the current proposal, we are focusing our attention on neurons in the CA1 region of the rat hippocampus, studied in the brain slice preparation. We are interested in how neuromodulators, normally released from diffuse fibers in the hippocampus, affect spike propagation and associated [Ca2+]i changes in the dendrites of pyramidal neurons. We will analyze the modulation of [Ca2+]i changes due to changes in the voltage profile of the spikes, modulation of dendritic Ca2+ channels, and control of the release of Ca2+ from internal stores. We also will analyze spike propagation and [Ca2+]i changes in interneurons. We will analyze these problems using a combination of high-speed fluorescence imaging of individual neurons filled with Ca2+-sensitive indicators, and whole-cell recording from cell bodies and dendrites. The electrical recordings directly reveal information about spike propagation at the site of recording. The imaging data give a more global picture of spike propagation in different parts of the neuron as well as directly revealing information about activity-dependent [Ca2+]i changes.